Nebulized Bacteriophages for Prophylaxis of Experimental Ventilator-Associated Pneumonia Due to Methicillin-Resistant Staphylococcus aureus

Prazák, J; Valente, Luca; Iten, Manuela; Grandgirard, Denis; Leib, Stephen L.; Jakob, Stephan M.; Hænggi, Matthias; Que, Yok-Ai; Cameron, David R.

doi:10.1097/ccm.0000000000004352

Cited by 26 publications

(21 citation statements)

References 12 publications

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“…Treatment with the nebulized phage cocktail resulted in a 70% survival rate at 48 hours; whereas untreated S. aureus infected rats all succumbed to the infection by this time. 90…”

Section: Staphylococcus Aureusmentioning

confidence: 99%

Reapproaching Old Treatments: Considerations for PK/PD Studies on Phage Therapy for Bacterial Respiratory Infections

Schmalstig

Freidy

Hanafin

et al. 2021

Clin Pharma and Therapeutics

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Antibiotic resistant bacterial respiratory infections are a significant global health burden, and new therapeutic strategies are needed to control the problem. For bacterial respiratory infections, this need is emphasized by the rise in antibiotic resistance and a lean drug development pipeline. Bacteriophage (phage) therapy is a promising alternative to antibiotics. Phage are viruses that infect and kill bacteria. Because phage and antibiotics differ in their bactericidal mechanisms, phage are a treatment option for antibiotic-resistant bacteria. Here, we review the history of phage therapy and highlight recent preclinical and clinical case reports of its use for treating antibiotic-resistant respiratory infections. The ability of phage to replicate while killing the bacteria is both a benefit for treatment and a challenge for pharmacokinetic (PK) and pharmacodynamic (PD) studies. In this review, we will discuss how the phage lifecycle and associated bidirectional interactions between phage and bacteria can impact treatment. We will also highlight PK/PD considerations for designing studies of phage therapy to optimize the efficacy and feasibility of the approach.

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“…Treatment with the nebulized phage cocktail resulted in a 70% survival rate at 48 hours; whereas untreated S. aureus infected rats all succumbed to the infection by this time. 90…”

Section: Staphylococcus Aureusmentioning

confidence: 99%

Reapproaching Old Treatments: Considerations for PK/PD Studies on Phage Therapy for Bacterial Respiratory Infections

Schmalstig

Freidy

Hanafin

et al. 2021

Clin Pharma and Therapeutics

View full text Add to dashboard Cite

show abstract

“…(iv) cream of phage preparations for skin infections. (v) injectable types of phage formulations [41,47,79]. (vi) phage infusion preparations may be considered for bloodstream infection [80,81].…”

Section: Phage Therapymentioning

confidence: 99%

“…In contrast, administration of bacteriophages by both the aerophages and IV phages rescued 91% of animals, which used to be greater than either monotherapy. Standard-of-care antibiotic linezolid saved 38% of animals [79]. The natural phages belonging to Caudovirales including order Siphoviridae, Myoviridae, and Podoviridae had been separated from the clinical strains of multidrug-resistant K. pneumoniae.…”

Section: Pneumoniaementioning

confidence: 99%

Therapeutic Efficacy of Bacteriophages

Ramasamy¹,

Dayanithi²

2021

Bacteriophages in Therapeutics

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Bacteriophages are bacterial cell-borne viruses that act as natural bacteria killers and they have been identified as therapeutic antibacterial agents. Bacteriophage therapy is a bacterial disease medication that is given to humans after a diagnosis of the disease to prevent and manage a number of bacterial infections. The ability of phage to invade and destroy their target bacterial host cells determines the efficacy of bacteriophage therapy. Bacteriophage therapy, which can be specific or nonspecific and can include a single phage or a cocktail of phages, is a safe treatment choice for antibiotic-resistant and recurrent bacterial infections after antibiotics have failed. A therapy is a cure for health problems, which is administered after the diagnosis of the diseases in the patient. Such non-antibiotic treatment approaches for drug-resistant bacteria are thought to be a promising new alternative to antibiotic therapy and vaccination. The occurrence, biology, morphology, infectivity, lysogenic and lytic behaviours, efficacy, and mechanisms of bacteriophages’ therapeutic potentials for control and treatment of multidrug-resistant/sensitive bacterial infections are discussed. Isolation, long-term storage and recovery of lytic bacteriophages, bioassays, in vivo and in vitro experiments, and bacteriophage therapy validation are all identified. Holins, endolysins, ectolysins, and bacteriocins are bacteriophage antibacterial enzymes that are specific. Endolysins cause the target bacterium to lyse instantly, and hence their therapeutic potential has been explored in “Endolysin therapy.” Endolysins have a high degree of biochemical variability, with certain lysins having a wider bactericidal function than antibiotics, while their bactericidal activities are far narrower. Bacteriophage recombinant lysins (chimeric streptococcal–staphylococcal constructs) have high specificity for a single bacterial species, killing only that species (lysin (CF-301) is focused to kill methicillin resistant Staphylococcus aureus (MRSA)), while other lysins have a broader lytic activity, killing several different bacterial species and hence the range of bactericidal activity. New advances in medicine, food safety, agriculture, and biotechnology demonstrate molecular engineering, such as the optimization of endolysins for particular applications. Small molecule antibiotics are replaced by lysins. The chapter discusses the occurrences of lytic phage in pathogenic bacteria in animals and humans, as well as the possible therapeutic effects of endolysins-bacteriophage therapy in vivo and in vitro, demonstrating the utility and efficacy of the therapy. Further developments in the bacteriophage assay, unique molecular-phage therapy, or a cocktail of phage for the control of a broad range of drug-resistant bacteria-host systems can promote non-antibiotic treatment methods as a viable alternative to conventional antibiotic therapy.

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“…Target bacteria that commonly cause respiratory problems and selection of bacteriophages can be quickly identified through screening method and by group of experts. Prophylactically administered bacteriophages decreased lung bacterial burdens and improved endurance of antibiotic resistant S. aureus infected animals with regards to ventilator-associated pneumonia [36]. It should be ensured to have the right selection of bacteriophages that target both the optimal bacteria and should be most effective against bacterial population growth.…”

Section: A Future For Phagesmentioning

confidence: 99%

Role of Phage Therapy in COVID-19 Infection: Future Prospects

Singh¹,

Gaur²,

Kumar³

2021

Bacteriophages in Therapeutics

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The pandemic of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was first reported in Wuhan City, China, in 2019. After that, the outbreak has grown into a global pandemic and definite treatment for the disease, termed coronavirus disease 2019 (COVID-19), is currently unavailable. The slow translational progress in the field of research suggests that a large number of studies are urgently required for targeted therapy. In this context, this hypothesis explores the role of bacteriophages on SARS-CoV-2, especially concerning phage therapy (PT). Several studies have confirmed that in addition to their antibacterial abilities, phages also show antiviral properties. It has also been shown that PT is effective for building immunity against viral pathogens by reducing the activation of NF kappa B; additionally, phages produce the antiviral protein phagicin. Phages can also induce antiviral immunity by upregulating expression of defensin 2. Phages may protect eukaryotic cells by competing with viral adsorption and viral penetration of cells, virus mediated cell apoptosis as well as replication. Moreover, by inhibiting activation of NF-κB and ROS production, phages can down regulate excessive inflammatory reactions relevant in clinical course of COVID-19. In this chapter, we hypothesize that the PT may play a therapeutic role in the treatment of COVID-19.

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Nebulized Bacteriophages for Prophylaxis of Experimental Ventilator-Associated Pneumonia Due to Methicillin-Resistant Staphylococcus aureus

Cited by 26 publications

References 12 publications

Reapproaching Old Treatments: Considerations for PK/PD Studies on Phage Therapy for Bacterial Respiratory Infections

Reapproaching Old Treatments: Considerations for PK/PD Studies on Phage Therapy for Bacterial Respiratory Infections

Therapeutic Efficacy of Bacteriophages

Role of Phage Therapy in COVID-19 Infection: Future Prospects

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